The goal of our activity is to understand the mechanisms underlying plastic changes in the human central nervous system and develop novel therapeutic approaches for recovery of function based on these advances. Most of our work has focused in plasticity of the human motor system and plasticity across sensory modalities (blindness). This year, we identified the window of opportunity for development of cross-modal plasticity in blind individuals. Individuals that became blind after age 13 years experience different and more modearate types of plastic changes. In the visual domain, we found that administration of 1hz repetitive transcranial magnetic stimulation can decrease the excitability of the human occipital cortex, a finding potentially relevant in the treatment of seizure disorders. In relation to use- dependent plasticity in motor cortex, we discovered that it is possible to block it by the administration of the NMDA-receptor antagonist dextromethorphan and by lorazepam, identifying LTP-like mechanisms as likely to operate in this form of plasticity. We also developed two ways to enhance use-dependent plasticity: by administration of d-amphetamine and also by concomitant administration of transacranial magnetic stimulation. In a collaborative effort with German investigators, we found that plasticity in the human motor cortex of amputees is larger in patients with phantom limb pain than in amputees without pain. In the area of rehabilitation after chronic stroke, we found that a rehabilitation treatment called "constraint induced therapy" appears to enhance the amount of use of the paretic arm long time after stroke. We have advanced in the understanding of the mechanisms,time- profile and site where plasticity takes place after a variety of disorders. Our future goals are to improve our understanding of the mechanisms underlying plasticity of function in humans and its functional relevance. On the basis of these mechanisms, we are starting to design and test interventions to improve motor disability after human diseases.